Zahra Barikbin, Md. Taifur Rahman, and Saif A. Khan* typical requirements of compartmentalization noted above. For example, designer surfactants can dictate and control biomolecule adsorption [11, 12] at the oil–water interface of an aqueous droplet or can catalyze a chemical reaction [13] inside the aqueous droplets. Mass-transfer between continuous phase and droplet or droplet-to-droplet may be employed in on-chip liquid-liquid extraction.[14, 15] Huck and co-workers reported mass transport between two static aqueous droplets via a surfactant bilayer to initiate an enzymatic reaction.[16] Ismagilov and co-workers have demonstrated that slow diffusion of water from a droplet of protein solution to another droplet containing brine via a fluorinated oil can controllably create supersaturation and lead to crystallization of the protein.[17] More recently this group showed that a reaction product from one droplet can produce a colorimetric signal in another reporter droplet by similar diffusive migration through the continuous oil phase.[18] We have recently demonstrated a microfluidic method in which an ionic liquid (IL) is introduced as a third fluid along with aqueous (Aq) and oil phases to generate IL–Aq bicompartmental droplets with the aqueous compartment partially or fully engulfed by the IL compartment.[19] In the partially engulfed droplet configuration, denoted as a ‘compound droplet’, the ionic liquid segment not only protects nearby aqueous droplets from coalescence,[20] but can also initiate and control chemical cross-talk with the aqueous compartment. In this configuration more direct and reliable intra-droplet chemical communication, which does not rely on transport through the continuous phase, is possible. Ionic liquids (ILs), liquid salts of organic cations and organic/inorganic anions, have attracted enormous attention due to their unique physical and chemical characteristics.[21, 22] Fluid properties such as viscosity, density, hydrophobicity, and even chemical reactivity can be predictably altered and tuned by appropriately selecting the cations and anions.[23, 24] It is this task-specific and tunable nature of ionic liquids that prompted us to examine their applicability as chemically interacting fluid-components in our compound droplet system. In this work, we report a droplet-based chemical analysis method (Figure 1a–d) possessing some intriguing features:(i) the unique physical and chemical characteristics of IL enables analyte (metal ion) to partition only between aqueous and ionic liquid compartments and not to the carrier fluorinated oil,(ii) analyte catalyzes the transformation of a substrate into a fluorescence emitting product in the ionic liquid compartment, and (iii) both the substrate and fluorescent